In natural biological systems, Zn2+ ion is found used as a structural factor, a catalytic factor, and a cocatalytic factor in many enzymes and proteins. In this article, we describe the design and synthesis of two classes of three-dimensional supramolecular complexes that are formed by assembly of multinuclear Zn2+ complex modules. The first group includes cuboctahedral capsules and trigonal prisms, in which Zn2+ ions are 5-coordinated and work as structural factors. The other class includes a supramolecular luminescent sensor for inositol 1, 4, 5-triphosphate (IP3) and its achiral model compound, cis, cis-1, 3, 5-cyclohexanetriol triphoshate (CTP3), which is formed by Ru-templated assembly of dimeric Zn2+ complexes, where Zn2+ ions work as recognition factors for three phosphates. This knowledge will be useful in designing novel supramolecular complexes and their applications in bioinorganic chemistry, bioinorganic chemistry, and other related scientific fields.
Organic compounds that bear perfluoroalkyl substituents such as CH2CH2CnF2n+1 (n=4-10) and the fluorine atom contents of which are higher than 60 wt% are soluble in perfluorocarbon like FC-72 (CF3 (CF2) 4CF3) but insoluble in common organic solvents. The unique nature has been applied to a simple and quick separation of organic products from a fluorous reagent, or a fluorous product from organic reagents, and to immobilization of a fluorous catalyst in the fluorous phase of a fluorous and organic biphase system. Using a fluorous silica gel column, fluorous compounds that bear only a single fluorous substituent can easily be separated from organic compounds but also themselves can be separated by HPLC depending upon their fluorine atom contents. Here we describe catalytic enantioselective reactions using fluorous BINOL and BINAP in the biphase system, separation of enantiomers of fluorous chiral alcohols and α-amino acid derivatives by HPLC with a β-cyclodextrin chiral column and a total synthesis of macrolactam bistratamide H using a new fluorous protecting group, 2-tris (pefluorodesyl) silylethoxycarbonyl.
A series of chiral aminophosphine ligands with N, N-disubstituted 2-diphenylphosphinoaniline backbone are designed and readily prepared from (R) -2- (methoxymethyl) pyrrolidine or (S) -prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation (AAA reaction) of 1, 3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral ligands are evaluated. Furthermore, chiral fluorous aminophosphine bearing two fluorous ponytails was prepared from (S) -prolinol. Chiral fluorous palladium catalyst from this ligand was easily reused in palladium-catalyzed AAA reaction with good enantioselectivity.
The identification of small molecule ligands for cellular proteins of biologically importance has not only provided new insights in biology, but has also provided organic chemists with the opportunity to create new synthetic molecules which efficiently regulate specific protein-protein interactions and biological processes. Small-molecule microarrays are recently developed as platforms to screen such small molecule ligands for proteins of interest. The small-molecule microarray technology is highly dependent on chemistry to immobilize small molecules on a variety of solid surfaces, and synthetic organic chemistry will continue to play a significant role in this field. This review covers the recent advances in the field with particular emphasis on the immobilization chemistry, as well as technical advances in the platform optimization and the successful applications of this platform.
More environmentally benign alternatives to current chemical processes, especially large-scale fundamental reactions, are highly desirable for many reactions. We have developed bulky diarylammonium pentafluorobenzenesulfonates 1a and 2a as mild and extremely active dehydration catalysts. In the presence of the catalysts, dehydrative cyclization of 1, 3, 5-triketones and ester condensation of carboxylic acids with equimolar amounts of alcohols are performed in heptane by heating at 80°C without the removal of water. We have also developed an efficient molybdenum oxide-catalyzed dehydrative cyclization of serine, threonine, and cysteine derivatives, which gives oxazolines and thiazolies. In the presence of molybdenum oxides, the reaction is carried out by heating at azeotropic reflux with the removal of water. Phosphate monoesters are synthesized from a mixture of phosphoric acid and alcohols in the presence of tributylamine. The reaction is promoted by nucleophilic bases such as N-butylimidazole. The hydroxyl groups of amino alcohols, such as 5'-hydroxyl group of 2', 3'-O-isopropylidene ribonucleosides, are phosphorylated selectively.
This article describes our recent studies on enzyme-and microorganism-mediated reactions, and application to the preparation of useful compounds based on the complementary chemo-enzymatic synthesis. First, lipase-catalyzed reactions were focused especially on the preparation of enantiomerically pure compounds, such as N-Boc-indoline-2-carboxylic acid, indanoxazolidinone and symbioramide. Next, the control of nitrile-hydrolyzing enzyme in Rhodococcus rhodochrous was summarized. A one-pot chemo-enzymatic transformation of aldehydes to amides was established. The third topic is the application of yeast-mediated asymmetric reduction of carbonyl compounds. The preparation of a couple of enantiomerically pure starting materials for natural product synthesis by the combination with chemical transformation was disclosed.
Recently, transition-metal promoted multi-component reactions have attracted much attention as powerful tools for onepot construction of complex molecules with high efficiency. For example, a number of couplings of three multiple-bonds via the formation of metallacycles using early transition metals have been reported. Late transition metal-catalyzed fourcomponent reactions involving catalytic cycles with combination of oxidative addition-reductive elimination have been investigated. Metathesis using the Grubbs catalysis is also embedded to the multi-component reactions.
A novel direct oxidative coupling reaction between carbonyl groups and indoles was recently developed. Total syntheses of highly functionalized natural products, (+) -hapalindole and (+) -welwitindolinone, were achieved using the new method. The present coupling strategy makes the synthesis of indole alkaloids highly concise and practical.
Here I report my projects at Dr. Jacobson's laboratory in National Institutes of Health. Conformationally locked nucleotides, N-methanocarba analogs and oxabicyclo [2, 2, 1] heptane analog, were prepared for hP2Y1 receptor. The most potent molecule is an N-methanocarba N6-methyl-2-iodo analogue (MRS-2500), which is the most potent antagonist selective for the P2Y1 receptor yet reported. I also succeeded in identifying the pairs of neoceptor-neoligand, which are pharmacologically orthogonal with respect to the native species.